MiR-200a ameliorates peritoneal fibrosis and functional deterioration in a rat model of peritoneal dialysis

Abstract

Peritoneal fibrosis is recognised as the main cause of the technical failure of peritoneal dialysis (PD), and currently, there are no specific and effective anti-fibrosis therapies. We have found that miR-200a is down-regulated in a rat model of PD-related peritoneal fibrosis (PF) and could inhibit transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells by target ZEB1/2. However, its treatment role in vivo is still largely unclear. In this study, we examined the therapeutic potential for miR-200a on PD-related PF in a rat model of PD induced by daily infusion of 4.25% dextrose-containing dialysate. Male Sprague–Dawley rats were divided into four groups: control group, PD group, PD + miR-agomir-NC group, and PD + miR-200a-agomir group ( n = 5 in each group). MiR-200a agomir was delivered into the peritoneum by intra-peritoneal injection on days 10 and 20 after PD. We found that treatment with miR-200a agomir significantly reduced the collagen volume fraction (CVF) of the peritoneum and prevented peritoneal dysfunction. The up-regulation of the EMT marker (decreased E-cadherin and increased α-smooth muscle actin) and extracellular matrix (fibronectin and collagen I) was significantly ameliorated by miR-200a in the PD + miR-200a-agomir group. Furthermore, we demonstrated that miR-200a inhibition of PF in vivo was associated with the suppression of ZEB1 and 2, which were proved to be the target of miR-200a in our previous study. In conclusion, results from the present study suggest that treatment with miR-200a may represent a novel and effective therapy for PD-related PF.

Effects of Uremic Clearance Granules on p38 MAPK/NF-κB Signaling Pathway, Microbial and Metabolic Profiles in End-Stage Renal Disease Rats Receiving Peritoneal Dialysis

“…Then, 4.25% glucose peritoneal dialysis solution (H20133286, Baite) (100 mL/kg/d) was injected into the abdominal cavity. 22 At the same time of PD, the rats in the UCG group were gavaged with UCG (5 g/kg/d) (CONSUN Pharmaceutical Co., Ltd.). 6 Rats in the Sham group and Model group were gavaged with the same volume of saline.…”

Intercellular communication in peritoneal dialysis

“…For instance, high-glucose (HG) treatment was shown to significantly upregulate the expression of the miR-199a-5p/214-3p gene cluster to induce downregulation of claudin-2 and E-cadherin related to EMT, whereas silencing of miR-199a-5p or miR-214-3p inhibited HG-induced mesothelial phenotypic transition, thereby reducing fibroblast formation ( Guo et al, 2020 ). Similarly, miR-153-3p ( Li D. et al, 2018 ), miR-129-5p ( Xiao et al, 2015 ), miR-145 ( Wu et al, 2019 ), and miR-200a ( Wei et al, 2019a ) target MMT to intervene in mesothelial-to-fibroblast transformation. The role of lncRNAs as paracrine-signaling mediators in the peritoneal membrane has attracted significant research attention.…”